This invention relates to a table-within-a-tablet pharmaceutical composition (hereinafter referred to as a dual-action tablet). The dual-action tablet gives a sustained dose of active ingredient followed by an immediate dose of active ingredient.
Depending upon the desired route of administration of the active material, pharmaceutical tablets may be produced in a variety of dosage forms that will either delay or prolong the release of the active material. The pharmacological effect of an active ingredient is typically correlated to its concentration in blood plasma of the organism. The dosage form determines how rapidly the active ingredient is released. In turn, the rate of release of active ingredient influences its blood plasma concentration. Optimal treatment often necessitates that a certain minimum effective concentration be maintained, at which concentration the active ingredient is able to exert its desired pharmacological effect on the organism. Ordinary capsules and tablets rapidly release the active ingredient, leading initially to a highly elevated concentration in plasma. However, the more quickly the active ingredient is eliminated from the organism's system, the more frequently must the active ingredient be administered to maintain the minimum effective concentration.
Many pharmaceutical compositions have been designed attempting to either prolong or delay the release of active ingredient in order to maintain a minimum effective concentration. A sustained release tablet is one which gives a continual release of drug from the time of administration. A delayed release tablet provides for a delay between the time of administration of active ingredient and its release.
The typical delayed release tablet dosage form uses enteric coated polymer systems to coat the tablet or capsule. However, the use of such pH dependent polymers in the enteric coating results in a dosage form that tends to perform erratically in humans due to variations in both gastric emptying times and the pH of gastric and intestinal fluid. Despite this, delayed release compositions may offer advantages, including: reducing the dosing regimen, reducing side effects, and targeting that portion of the alimentary canal in which the active ingredient will be released.
In contrast to delayed release tablets, sustained release tablets extend the duration of drug level in the body. Many different names are associated with sustained release products, such as timed release and prolonged release. Typical sustained release formulations are coated tablets containing an active in a polymeric matrix or coated granules of the active contained in capsules. Some of these dosage forms are designed to release portions of the active at different places in the gastrointestinal tract. Other sustained release compositions slowly dissolve or erode, allowing a gradual release of active. Sustained release compositions may offer the following therapeutic advantages: reducing side effects, reducing drug accumulation with chronic dosing, and reducing fluctuations in drug level.
Many delayed release and substained release formulations are described in the pharmaceutical literature. For example, U.S. Pat. No. 3,558,768 issued Jan. 26, 1971 describes a sustained release tablet while U.S. Pat. No. 2,887,438 issued May 19, 1959 describes a tablet alleged to have the combined properties of both delayed release and sustained release.
A disadvantage of some delayed release and/or sustained release formulations is that for active ingredients that are water soluble and have half lives of less than about two hours, it is difficult to maintain the minimum effective concentration of active ingredient in the blood plasma for a period longer than about eight hours after administration. (As used herein, the term "half life" means the time taken to decrease the concentration of drug in the blood plasma of the organism by about one half.) This may preclude a more convenient twice-a-day dosage regimen for an active material. Another disadvantage, particularly for compositions that rely upon enteric coatings for sustained or delayed release, is that the release of active ingredient may depend on the pH of the gastrointestinal environment. This may lead to erratic and unpredictable release of the active ingredient.